Safety and Efficacy of Vicriviroc (MK-7690) in Combinatio... | NCT03631407

ID	Type	Description	Link
MK-7690-046	Other Identifier	MSD

Label	Type	Description	Intervention Names
Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Experimental	Participants receive vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).	Drug: Vicriviroc Biological: Pembrolizumab
Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Experimental	Participants receive vicriviroc 250 mg tablets PO QD of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute IV infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).	Drug: Vicriviroc Biological: Pembrolizumab

Name	Type	Description	Arm Group Labels	Other Names
Vicriviroc	Drug	Vicriviroc tablets administered orally, QD at dose level 1 or 2.	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg) Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)

Measure	Description	Time Frame
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)	Objective response rate (ORR) was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator. ORR was estimated and analyzed using Clopper-Pearson interval.	Up to ~32 months
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	DLTs were assessed during the first cycle (21 days) & were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia of any duration, Gr 3 thrombocytopenia associated with bleeding; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for >72 hours); Gr 3 or 4 febrile neutropenia; inability to receive ≥75% of the planned vicriviroc dose because of drug-related tolerability; drug-related toxicity that caused a >2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is >3× upper limit of normal (ULN) & an elevated total bilirubin value >2× ULN & an alkaline phosphatase value <2× ULN, in which no alternative reasons were found.	Up to Day 21 of Cycle 1 (each cycle is 21 days)
Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.	Up to ~28 months
Number of Participants Who Discontinued Study Treatment Due to an AE

Measure	Description	Time Frame
Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)	An objective response rate was defined as the percentage of participants who experienced an immune-based complete response (iCR: disappearance of all target lesions) or immune-based partial response (iPR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced an iCR or iPR using immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) per investigator was presented. ORR was estimated and analyzed using Clopper-Pearson interval.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have a histologically proven locally advanced unresectable or metastatic CRC.
Have locally confirmed MSS CRC.
Have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan, and have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study intervention.
Male participants must agree to use contraception and refrain from donating sperm for at least 120 days after the last dose of study intervention.
Female participants must be not pregnant and not breastfeeding. Further, a female participant must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention.
Have adequate organ function.

Exclusion Criteria:

Have a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Have severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study interventions.
Have an active autoimmune disease requiring systemic treatment in the past 2 years, except vitiligo or resolved childhood asthma/atopy.
Have a history of vasculitis.
Have an active infection requiring systemic therapy.
Have symptomatic ascites or pleural effusion.
Have interstitial lung disease requiring oral or IV glucocorticoids.
Have a history of pneumonitis (noninfectious) that required steroids, or has current pneumonitis.
Have a known history of human immunodeficiency virus (HIV) infection.
Have a known history of hepatitis B or known active hepatitis C virus infection.
Have a known history of active tuberculosis (TB; Bacillus tuberculosis).
Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study interventions hazardous, or make it difficult to monitor adverse events.
Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with study requirements.
Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
Are a WOCBP who has a positive urine pregnancy test within 72 hours before randomization or treatment allocation.
Have undergone major surgery and have not recovered adequately from any toxicity and/or complications from the intervention before starting study intervention.
Have a seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g., CNS malignancy or toxoplasmosis).
Have known gastrointestinal (GI) disease such as esophageal, gastric, or duodenal ulceration or inflammatory bowel disease, or history of GI surgery.
Are using any drug (therapeutic or recreational), or withdrawal thereof, that poses an increased risk of convulsions.
Have had an allogeneic tissue/solid organ transplant.
Have received prior therapy with vicriviroc or other CCR5 antagonist (e.g., maraviroc) or have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent.
Have been treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
Have received prior systemic anticancer therapy, including investigational agents, or has used an investigational device within 28 days before the first dose of study intervention.
Have received prior radiotherapy (not to target lesions) within 2 weeks of start of study intervention.
Are expected to require any other form of antineoplastic therapy while on study.
Have a diagnosis of immunodeficiency, is receiving chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or is taking any other form of immunosuppressive medication within 7 days before the first dose of the study intervention.
Have received a live-virus vaccine within 30 days before the first dose of the study intervention.
Are currently participating in or have participated in a study of an investigational agent, or have used an investigational device within 28 days before the first dose of study intervention.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Honor Health ( Site 0103)		Scottsdale	Arizona	85258	United States
California Cancer Associates for Research & Excellence ( Site 0100)

PubMed Identifier	Type	Citation	Retractions
38942693	Result	Bessudo A, Haseeb AM, Reeves JA, Zhu X, Wong L, Giranda V, Suttner L, Liu F, Chatterjee M, Sharma S. Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Microsatellite Stable Colorectal Cancer. Clin Colorectal Cancer. 2024 Sep;23(3):285-294. doi: 10.1016/j.clcc.2024.05.003. Epub 2024 May 13.

ID	Title	Description
FG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 7, 2019

ID	Title	Description
BG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
BG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00021 BG00120 BG00241

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

Objective response rate (ORR) was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator. ORR was estimated and analyzed using Clopper-Pearson interval.

The analysis population consisted of all participants who received at least 1 dose of study treatment, and had a baseline scan with measurable disease per investigator's assessment per RECIST 1.1.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to ~32 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Units	Counts
Participants	OG00020 OG00120

Title

Denominators

Categories

Title	Measurements
	OG0005.0(0.1 to 24.9) OG0015.0(0.1 to 24.9)

Primary

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

DLTs were assessed during the first cycle (21 days) & were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia of any duration, Gr 3 thrombocytopenia associated with bleeding; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for >72 hours); Gr 3 or 4 febrile neutropenia; inability to receive ≥75% of the planned vicriviroc dose because of drug-related tolerability; drug-related toxicity that caused a >2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is >3× upper limit of normal (ULN) & an elevated total bilirubin value >2× ULN & an alkaline phosphatase value <2× ULN, in which no alternative reasons were found.

The analysis population consisted of all treated participants who received at least one dose of study drug and finished Cycle 1 without a DLT or experienced a DLT in Cycle 1.

Posted

Count of Participants

Participants

Up to Day 21 of Cycle 1 (each cycle is 21 days)

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001

Primary

Number of Participants Who Experienced an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.

The analysis population consisted of all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

Up to ~28 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Primary

Number of Participants Who Discontinued Study Treatment Due to an AE

The analysis population consisted of all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

Up to ~25 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)

An objective response rate was defined as the percentage of participants who experienced an immune-based complete response (iCR: disappearance of all target lesions) or immune-based partial response (iPR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced an iCR or iPR using immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) per investigator was presented. ORR was estimated and analyzed using Clopper-Pearson interval.

The analysis population consisted of all participants who received at least 1 dose of study treatment, and had a baseline scan with measurable disease per investigator's assessment per modified iRECIST.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to ~32 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

Progression-Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

The analysis population consisted of all participants who received at least 1 dose of study treatment, and had a baseline scan with measurable disease per investigator's assessment per RECIST 1.1.

Posted

Median

95% Confidence Interval

Months

Up to ~32 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

PFS Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)

PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per modified iRECIST or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

Posted

Median

95% Confidence Interval

Months

Up to ~32 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

Overall Survival (OS)

OS is defined as the time from the first dose of study treatment until death from any cause.

The analysis population consisted of all participants who received at least 1 dose of study treatment, and had a baseline scan with measurable disease per investigator's assessment.

Posted

Median

95% Confidence Interval

Months

Up to ~32 months

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Units	Counts
Participants

Secondary

Plasma Area Under the Concentration Time-Curve From 0 to 8 Hours (AUC 0-8hrs) of Vicriviroc

Plasma vicriviroc concentration was quantified for each arm to determine AUC 0-8hrs, defined as the area under the concentration vs. time curve for vicriviroc from 0 to 8 hours.

The analysis population consisted of all participants who received at least 1 treatment and who contributed blood samples for analysis of AUC 0-8hrs. Per protocol, AUC 0-8hrs was calculated for the participants who had concentration values.

Posted

Geometric Mean

Geometric Coefficient of Variation

hr*ng/mL

Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

Maximum Observed Plasma Concentration (Cmax) of Vicriviroc

Plasma vicriviroc concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of vicriviroc in plasma.

The analysis population consisted of all participants who received at least 1 treatment and who contributed blood samples for analysis of Cmax. Per protocol, Cmax was calculated for the participants who had concentration values.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Secondary

Trough Plasma Concentration (Ctrough) of Vicriviroc

Plasma vicriviroc concentration was quantified for each arm to determine Ctrough, defined as the minimum plasma concentration of vicriviroc observed after administration and just before the subsequent dose.

The analysis population consisted of all participants who received at least 1 treatment and who contributed blood samples for analysis of Ctrough. Per protocol, Ctrough was calculated for the participants who had concentration values.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose, and 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1; Cycle 3 Day 21.

ID	Title	Description
OG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).
OG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Visual field defect	Eye disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected20 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events1 affected20 at risk
Death	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk
Ill-defined disorder	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Coccidioidomycosis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Pneumonia	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Sepsis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected20 at risk
Stomal hernia	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Blood bilirubin increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk
Encephalopathy	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Lethargy	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Confusional state	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected20 at risk
Female genital tract fistula	Reproductive system and breast disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected20 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0011 events1 affected20 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0018 events6 affected20 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events1 affected20 at risk EG0014 events3 affected20 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0005 events5 affected20 at risk EG0013 events3 affected20 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0007 events7 affected20 at risk EG0013 events3 affected20 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0016 events4 affected20 at risk
Flatulence	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0007 events6 affected20 at risk EG0016 events5 affected20 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0006 events5 affected20 at risk EG0014 events4 affected20 at risk
Chills	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk
Fatigue	General disorders	MedDRA 24.0	Systematic Assessment	EG0007 events6 affected20 at risk EG0018 events8 affected20 at risk
Pyrexia	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0006 events3 affected20 at risk EG0018 events6 affected20 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected20 at risk EG0017 events7 affected20 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0018 events8 affected20 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0013 events3 affected20 at risk
Blood bilirubin increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk
Blood creatinine increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0004 events4 affected20 at risk EG0014 events3 affected20 at risk
Weight decreased	Investigations	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected20 at risk EG0012 events2 affected20 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0014 events4 affected20 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0013 events2 affected20 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0017 events3 affected20 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0004 events4 affected20 at risk EG00110 events4 affected20 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0014 events2 affected20 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0014 events3 affected20 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0014 events3 affected20 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0012 events2 affected20 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk
Dizziness	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0017 events6 affected20 at risk
Dysgeusia	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected20 at risk
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected20 at risk
Anxiety	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Confusional state	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Insomnia	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0015 events5 affected20 at risk
Nocturia	Renal and urinary disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected20 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected20 at risk EG0013 events3 affected20 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected20 at risk EG0012 events2 affected20 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected20 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0004 events4 affected20 at risk EG0016 events4 affected20 at risk

ID	Term
D015179	Colorectal Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body
D013132	Spinocerebellar Degenerations

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases
D002526	Cerebellar Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D013118	Spinal Cord Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).	19	21	12	20	14	20
EG001	Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)	Participants received vicriviroc 250 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg administered as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).	17	20	10	20	19	20